TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24112	72559;72560;72561	chr2:178573798;178573797;178573796	chr2:179438525;179438524;179438523
N2AB	22471	67636;67637;67638	chr2:178573798;178573797;178573796	chr2:179438525;179438524;179438523
N2A	21544	64855;64856;64857	chr2:178573798;178573797;178573796	chr2:179438525;179438524;179438523
N2B	15047	45364;45365;45366	chr2:178573798;178573797;178573796	chr2:179438525;179438524;179438523
Novex-1	15172	45739;45740;45741	chr2:178573798;178573797;178573796	chr2:179438525;179438524;179438523
Novex-2	15239	45940;45941;45942	chr2:178573798;178573797;178573796	chr2:179438525;179438524;179438523
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-131
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.475
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/E	None	None	0.999	N	0.574	0.437	0.326881540566	gnomAD-4.0.0	1.59852E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8714E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.3985	ambiguous	0.5008	ambiguous	-0.462	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
K/C	0.6975	likely_pathogenic	0.7829	pathogenic	-0.627	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
K/D	0.675	likely_pathogenic	0.7528	pathogenic	0.021	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/E	0.1695	likely_benign	0.2261	benign	0.137	Stabilizing	0.999	D	0.574	neutral	N	0.45930836	None	None	N
K/F	0.8553	likely_pathogenic	0.9134	pathogenic	-0.189	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/G	0.5664	likely_pathogenic	0.6649	pathogenic	-0.804	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
K/H	0.3319	likely_benign	0.4096	ambiguous	-0.964	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/I	0.4655	ambiguous	0.5687	pathogenic	0.411	Stabilizing	1.0	D	0.799	deleterious	D	0.522266547	None	None	N
K/L	0.4857	ambiguous	0.6043	pathogenic	0.411	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
K/M	0.301	likely_benign	0.3717	ambiguous	0.055	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/N	0.4899	ambiguous	0.5978	pathogenic	-0.447	Destabilizing	1.0	D	0.732	prob.delet.	N	0.477398262	None	None	N
K/P	0.9408	likely_pathogenic	0.9509	pathogenic	0.15	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/Q	0.1213	likely_benign	0.1481	benign	-0.44	Destabilizing	1.0	D	0.717	prob.delet.	N	0.494213154	None	None	N
K/R	0.0839	likely_benign	0.0921	benign	-0.445	Destabilizing	0.999	D	0.537	neutral	N	0.485748387	None	None	N
K/S	0.3494	ambiguous	0.439	ambiguous	-1.056	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	N
K/T	0.1419	likely_benign	0.1784	benign	-0.733	Destabilizing	1.0	D	0.783	deleterious	N	0.425177144	None	None	N
K/V	0.3626	ambiguous	0.4516	ambiguous	0.15	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
K/W	0.8351	likely_pathogenic	0.888	pathogenic	-0.119	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/Y	0.7048	likely_pathogenic	0.7877	pathogenic	0.174	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.